TRPA1 as a therapeutic target for nociceptive pain

ABSTRACT

Introduction

Chronic pain affects approximatively 30–50% of the population globally. Pathologies such as migraine, diabetic neuropathy, nerve injury and treatment with chemotherapeutic agents, can induce chronic pain. Members of the transient receptor potential (TRP) channels, including the TRP ankyrin 1 (TRPA1), have a major role in pain.

Areas covered

We focus on TRPA1 as a therapeutic target for pain relief. The structure, localization, and activation of the channel and its implication in different pathways to signal pain are described. This paper underlines the role of pharmacological interventions on TRPA1 to reduce pain in numerous pain conditions. We conducted a literature search in PubMed up to and including July 2020.

Expert opinion

Our understanding of the molecular mechanisms underlying the sensitization of central and peripheral nociceptive pathways is limited. Preclinical evidence indicates that, in murine models of pain diseases, numerous mechanisms converge on the pathway that encompasses oxidative stress and Schwann cell TRPA1 to sustain chronic pain. Programs to identify and develop treatments to attenuate TRPA1-mediated chronic pain have emerged from this knowledge. Antagonists explored as a novel class of analgesics have a new and promising target in the TRPA1 expressed by peripheral glial cells.

KEYWORDS:

• Inflammatory pain
• neuropathic pain
• nociception
• Transient Receptor Potential (TRP) channels
• TRP ankyrin 1 (TRPA1)

Article highlights

• TRP channels belong to a large family of ion channels with pleiotropic roles in a variety of cells and systems.

• The TRPA1 channel is widely studied in the mechanism/process of inflammatory, neuropathic, cancer, and migraine pain.

• In addition to the peripheral nervous system, the TRPA1 channel is localized in several non-neuronal cell types.

• Endogenous molecules produced by various pathological conditions, such as reactive oxygen (ROS), nitrative (RNS), and carbonylic (RCS) species, activate TRPA1 to sustain chronic pain.

• TRPA1 activation leads to pain responses.

This box summarizes key points contained in the article.

Declarations of interest

F De Logu, P Geppetti and R.Nassini are founding scientists of FloNext Srl. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Disclosure statement

No potential conflict of interest was reported by the authors.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC, IG 19247 and AIRC MFAG, 13336) and Fondazione Cassa di Risparmio di Firenze, Italy (R.N.); European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 835286) (P.G.).